The objective of this project is to determine the humoral and cellular mechanisms involved in the pathogenesis of human periodontal disease(s). The spectrum of local B cell responses to bacteria and bacterial antigens, which are believed to induce and maintain the inflammatory process, is assessed at the single cell level by the enzyme-linked immunospot (ELISPOT) test. This method is also being used in determining the contribution of autoreactive B cells in inflamed gingivae by enumerating immunoglobulin isotype and subclass-specific spot forming cells to various types of human collagens and rheumatoid factors. In addition, natural killer cell regulation of B cell differentiation in inflamed gingivae is also being studied. Preliminary data suggests that local (but not systemic) production of autoantigens occurs in adult periodontitis.